The research plan is a multidisciplinary multisite set of highly interrelated research components to study the characteristics of tolerance to alcohol in human subjects from a psychobiological perspective. Goals: (1) to determine those psychobiological variables that distinguish drivers high in alcohol tolerance, and (2) to search for possible multivariate indicators of tolerance. Even at blood alcohol concentrations (BAC) well above the legal limit (0.10%), such drivers may not manifest typical signs of intoxication and thus are rarely arrested for DUI/DWI. A unique opportunity to examine high tolerant drivers is available through a new NIAAA grant to the Co-principal investigators. At roadside surveys, 42,000 drivers will be screened for BAC using the new "passive sensor." A subsample (n=320) from the spectrum of drinking drivers will be invited to serve as subjects. The core component (Component I) will study the subjects with varying degrees of alcohol tolerance in 3 experiments in which they are tested at their usual social dose, at predetermined experimental doses, and under differing conditions of alcohol expectancy. Each of the 5 components will collect data in distinct areas: Component II - Behavioral/psychological; Component III - Phenomenological; Component IV - Pharmacokinetics and genetics of metabolism. Between-subject specific aims: determine extent to which high vs. low tolerant drinkers: (1) differ on psychobiological variables measured at each of four BACs (0.00, 0.05, 0.10, & 0.15%), (2) show impairment at a given BAC, (3) need a larger dose to produce the same effect, (4) differ regarding amount of alcohol and resulting BAC needed to reach their "usual level of intoxication," (5) overestimate rather than underestimate their actual BACs, and (6) show alcohol expectancy effect. Within-subject specific aims: determine (7) a self-paced, baseline, "usual high;" (8) alcohol sensitivity, acute tolerance, and degree of chronic tolerance; and (9) validity of ratings on clinical signs of intoxication and field sobriety tests obtained under real-world conditions at roadside. Long-term objectives: Data will be obtained from the same motorist/subjects, ranging from roadside BAC, ratings on clinical signs of intoxication, and field sobriety tests; to other psychological, physiological, and biochemical measures including alcohol metabolism and genetic factors; plus data concerning personality, attitudes, drug use, and lab experiments provide the basis for strong potential advance in our understanding of chronic alcohol tolerance. Active direct intervention is planned for the high tolerant subjects. Results provide basis for developing future prevention strategies for high tolerant drinkers in general population.